title: Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene.
abstract: In mice lacking the nociceptin (or orphanin FQ) receptor gene, when 10 mg/kg of morphine was subcutaneously given, a potent analgesia in the tail pinch test was observed. The analgesic effect of morphine was equivalent among wild-type, heterozygous and homozygous mutant mice. When morphine was given to such mice in a dose of 10 mg/kg once per day for 5 days, wild-type and heterozygous mice showed marked tolerance or reduction in the morphine analgesia on the 5th day, while homozygous mice showed only 50% reduction in the peripheral analgesia of morphine. These findings suggest that nociceptin or its receptor plays important roles in the in vivo mechanism for the development of morphine tolerance.
authors.affiliation: Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Japan. ueda@net.nagasaki-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Ueda
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Tokuyama
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Nishi
authors.forename: H
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D004361:Drug Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009154:Mutation; D010147:Pain Measurement / Q000187:drug effects; D011957:Receptors, Opioid / Q000235:genetics*; D000094942:Nociceptin Receptor
chemical_list: D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D009020:Morphine; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse